Transient Dux expression facilitates nuclear transfer and induced pluripotent stem cell reprogramming.

Lei Yang, Xuefei Liu, Lishuang Song, Anqi Di, Guanghua Su, Chunling Bai, Zhuying Wei, Guangpeng Li

EMBO reports 2020 Sep 03

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Cloned animals generated by somatic cell nuclear transfer (SCNT) have been reported for many years; however, SCNT is extremely inefficient, and zygotic genome activation (ZGA) is required for SCNT-mediated somatic cell reprogramming. To identify candidate factors that facilitate ZGA in SCNT-mediated reprogramming, we performed siRNA-repressor and mRNA-inducer screenings, which reveal Dux, Dppa2, and Dppa4 as key factors enhancing ZGA in SCNT. We show that direct injection of ZGA inducers has no significant effect on SCNT blastocyst formation; however, following the establishment of an inducible Dux transgenic mouse model, we demonstrate that transient overexpression of Dux not only improves SCNT efficiency but also increases that of chemically induced pluripotent stem cell reprogramming. Moreover, transcriptome profiling reveals that Dux-treated SCNT embryos are similar to fertilized embryos. Furthermore, transient overexpression of Dux combined with inactivation of DNA methyltransferases (Dnmts) further promotes the full embryonic development of SCNT-derived animals. These findings enhance our understanding of ZGA-regulator function in somatic reprogramming. © 2020 The Authors.

Citation

Lei Yang, Xuefei Liu, Lishuang Song, Anqi Di, Guanghua Su, Chunling Bai, Zhuying Wei, Guangpeng Li. Transient Dux expression facilitates nuclear transfer and induced pluripotent stem cell reprogramming. EMBO reports. 2020 Sep 03;21(9):e50054